Project Summary/Abstract Meningococcal disease caused by the bacterial pathogen Neisseria meningitidis is responsible for significant morbidity and mortality worldwide. Preventing meningococcal disease is of particular public health importance because of the sudden onset of symptoms, rapid progression, and high case fatality even among previously healthy individuals. Serogroup B meningococcal (MenB) disease has caused outbreaks in multiple countries and the US, where several outbreaks occurred on college campuses in recent years. Teens and young adults are one of the groups at highest risk of invasive disease. In 2014 and 2015, two novel MenB vaccines, Bexsero (4CMenB, GSK) and Trumenba (rLP2086, Pfizer) were licensed in the US for 10-25 year olds. The extent to which these vaccines induce broadly protective, persistent immunity is unknown, limiting our ability to understand the kinetics of the immune response and to develop optimal vaccination strategies. In addition, no studies have evaluated these two vaccines using the same measures of immunity against the same disease-causing MenB isolates. We aim to advance the field of vaccinology and to improve efforts to prevent deadly cases of MenB disease by evaluating both the short-term and long-term immunogenicity of these MenB vaccines and by investigating the breadth of immunity induced against the diversity of MenB strains that cause disease. To achieve these aims, we will conduct clinical epidemiological research using a novel serum bank that we collected from teens and young adults during two of the first studies of Bexsero immunogenicity in the US, and we will extend the period of follow up among this unique cohort. In addition, we will use similar methods to enroll young adults into a prospective longitudinal study to evaluate Trumenba immunity. To evaluate immune responses, we will conduct serum bactericidal antibody assays using externally-derived human complement (hSBA) and a recently developed serum bactericidal antibody assay using intrinsic human complement (iSBA) to investigate how broadly immunogenic both vaccines are against a collection of dozens of MenB isolates and whether immunity persists long term. We will then develop statistical models to evaluate hSBA and iSBA responses and the relationship between these markers of functional immunity over time. We aim to rigorously and simultaneously evaluate Bexsero and Trumenba vaccine- induced immunity against the same panel of MenB strains. Meningococcal B vaccines are critical tools for the prevention of invasive meningococcal disease. Our research will combine new epidemiologic data, novel laboratory methods, and statistical models to generate urgently needed evidence that will increase our understanding of vaccine-induced immunity. Our results can be used to inform vaccination policy so that effective, targeted vaccination strategies can be designed and implemented.